The present invention relates to a chemically sensitive transducer for the selective detection of the chemical properties of a fluid, and more specifically, to a transducer with a measuring electrode overlaid with a membrane that is sensitive to the chemical properties. This electrode is coupled to the gate of a field-effect transistor. The transducer has an encapsulation which isolates the entire transducer except for the membrane from the fluid.
The term "chemically sensitive" refers to an ion or gas sensitive property, a sensitivity to enzyme substrates, to antibodies/antigens or to hydride-forming DNA/RNA groups. Depending on their sensitivity, transducers can be utilized in medicine, for example in blood analysis, in clinical chemistry, for therapy control, hormone determination, infection and tumor diagnoses, as well as in fermentation control, food and environment analyses and process control.
A chemically sensitive transducer is known from EP-B-0 065 350, in which the gate of a field-effect transistor is connected via a laterally abutting conductor to an allocated measuring electrode disposed on the same side of the substrate. The field-effect transistor is provided in a semiconductor substrate. The measuring electrode is provided with a membrane, (i.e., a coating) which is sensitive to the chemical property to be determined and which is applied by electroplating, sputtering or vapor deposition. The field-effect transistor is encapsulated against the fluid that is to be examined by a protective layer composed of an epoxin resin or rubber.
Immersing a transducer of this design in the fluid to be examined yields, due to the ion exchange reactions between the electro-active substance of the membrane and the fluid at the gate electrode of the field-effect transistor, a potential which influences the channel conductivity of the field-effect transistor. Potentiometric or ammetric measurement permits obtaining a corresponding output signal proportional to the concentration of the parameter to be measured.
Other chemically sensitive transducers are known from EP-A-0 302 228, EP-B 0 078 590 and U.S. Pat. No. 4,514,276.
Although the voltage produced by the ion exchange reaction lies in the mV range, the non-reactive load capacity of the membrane, however, lies in the pA to fA range. When working with such low charge quantities, it is important that all interfering influences, in particular those of an electric or thermal nature, be prevented, a point for which the above-cited publications provide no measures. Another problem with the known transducers is that they can only be utilized for the determination of those chemical properties to which the membranes, which can be applied onto the measuring electrode with the aforementioned processes, are sensitive.
An object of the present invention is to provide a chemically sensitive transducer featuring higher sensitivity in comparison to known chemically sensitive transducers and which, at the same time, is insensitive to electric influences and temperature fluctuations. The transducer should also be able to be designed to be sensitive to properties that can be detected only with membrane substances of little stability.
These and other objects are provided by the present invention which provides a chemically sensitive transducer for selectively determining a chemical property of a fluid and providing a measurement signal to an amplifying circuit. The transducer has a measuring electrode coupled to the amplifying circuit and provides a measurement signal to the amplifying circuit. A membrane covers the measuring electrode, this membrane being sensitive to a specified chemical property. A carrier plate, with first and second sides, has the measuring electrode arranged on its first side and the amplifying circuit on its second side. The carrier plate has a conductor extending between the first and second sides which electrically couples the measuring electrode and the amplifying circuit.
The arrangement of the measuring electrode and the amplifying circuit on the opposite sides of a carrier plate with contact being made through the carrier plate yields, with small overall transducer dimensions and unrestricted possible design with regard to the size and number of measuring electrode surfaces, the shortest distances between the measuring electrode and the corresponding amplifying circuit with an accordingly high signal/noise ratio. In this manner, the transducer of the present invention increases its sensitivity in comparison to conventional transducers. Furthermore, a largely free choice in the design of the measuring problems is allowed by the present invention. In particular, all types of membranes, such as those used with conventional ion-selective electrodes, can be utilized.
Furthermore, the amplifying circuit can also be designed with very different techniques. For example, the transducer can be realized cost-effectively even in small quantities with the hybrid technique or thin film technique.
In an embodiment of the invention, the carrier plate consists of an insulating material, which may be, for example SiO.sub.2, a ceramic material such Al.sub.2 O.sub.3, glass, an epoxy resin or a plastic material. In this manner, the carrier plate not only ensures required stability, where there is little thickness, but also shields the amplifying circuit reliably from environmental influences. A ceramic material is suited, for example, for application of the measuring electrode material, the conducting layer and other conductor channels with the thick film technique.
In an embodiment of the invention, a conducting layer is arranged between the amplifying circuit and the carrier plate, which can be used at the same potential as the measuring electrode. This results in active shielding of the high impedance input signal from electric interference fields, thereby further improving the signal/noise ratio, and reducing the limit of sensitivity of the transducer and raising its speed of response as well as improving cross-talk behavior in a transducer with several channels. Further input capacitances are substantially eliminated.
In an embodiment of the invention, the electric connection (the conductor) between the measuring electrode and the field-effect transistor in the amplifying circuit is provided by a borehole extending completely through the carrier plate. This borehole preferably has a diameter of less than 0.1 mm and is coated at least on its sidewalls with a conducting material. This embodiment of the present invention has the advantage that, because of the small cross-section of the borehole, stationary or weakly moving fluids can not reach the amplifying circuit due to their surface tension even if the opening of the borehole were uncovered.
In an embodiment of the invention, the measuring electrodes, the conductor running through the carrier plate and if required, the conducting layer, are made of a material which is chemically inert to the fluid to be examined, so that it does not react with the fluid. In particular, practically any adjuvants (solvents, reducing and oxidating agents, radicals for couplings and polymerizings) may be employed for applying the membrane. Such materials are, by way of illustration, gold, platinum, silver, palladium (or their alloys) or a conductive polymer, such as polypyrrol.
In an embodiment of the invention, a mask plate disposed on the carrier plate restricts the area of the measuring electrode. This has the advantage that a trough-like receptacle with a defined base area is formed for applying the membrane onto the measuring electrode so that there is a corresponding expansion in the membrane and its thickness can be determined by simple dosing of the fluid. In this manner, it also becomes possible for the user himself to lay on the membrane with sufficient precision, which is necessary when sensitive materials and materials of little biological stability such as enzymes and antibodies are to be employed as membranes. Furthermore, it becomes possible to reuse transducers by removing spent membranes and replacing them with new ones. Membranes that can be put on by the user can be applied by means of electrochemical reactions or in a dissolved state. Furthermore, the mask plate may also be removable and therefore is replaceable. The mask plate may be arranged on the transducer only for the purpose of applying the membrane or the membrane surface may be varied by disposing mask plates of different design.
In an embodiment of the invention, the mask plate covers the borehole. This is useful for additional protection of the amplifying circuit provided in the encapsulment.
In an embodiment of the invention, an insulating layer covers the borehole, this insulating layer being provided between the mask plate and the carrier plate. The insulating layer further seals the conductor running through the carrier plate. The insulating layer may be made of SiO.sub.2, polyamide, epoxy resin, aluminum oxide or a silicon resin.
In an embodiment of the invention, the mask plate and the covering encapsulating the amplifying circuit are also made of the same material as the carrier plate. In this way, mechanical tension, like that which can lead to leakage due to temperature fluctuations at different thermal expansion coefficients, can be avoided. Furthermore, a ceramic makes a good electric insulator and is chemically inert, i.e. it does not react with the fluid to be examined and is physiologically indifferent.
The high pressure filling of the transducer encapsulation with an inert gas, as provided in an embodiment of the invention, is an additional measure that protects the amplifying circuit against penetration of water vapor and prevents oxidation of the electronic components, for example in autoclaving processes as can be conducted with temperature stable sensors.
In an embodiment of the invention, the transducer is provided with at least one pair of differential sensors having an active measuring electrode and an inactive measuring electrode. This circumvents the necessity of having an external reference electrode, which, however, can be employed at any time with the transducer of the present invention. The sensor channels in each case comprise a pair of sensors, the potential of which is determined in relation to a reference dissolving contact and are subtracted from one each other. One electrode surface is covered with the desired membrane and the other with the same, but "carrier-free" mixture. The term "carrier-free" means that the membrane, or the layer, does not have the sensitive component. Due to the formation of a differential, the instability of the potential of the reference dissolving contact and the unspecified matrix effect of the membranes like that produced, for example, by the diffusion of lipophile blood fats, is eliminated.
Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.